Platelet-activating factor-induced microvascular dysfunction: role of adherent leukocytes.
Platelet-activating factor (PAF) has been implicated in the pathogenesis of intestinal mucosal injury associated with endotoxemia, inflammation, allergic reactions, and ischemia-reperfusion. Although it is generally held that PAF initiates mucosal injury by enhancing transcapillary fluid and protein exchange, the effects of PAF on the intestinal microvasculature have not been defined to date. In this study we examined the influence of local intrarterial infusions of PAF (4, 20, and 40 ng/min) on intestinal transcapillary, lymphatic, and transmucosal water and protein fluxes. All of these parameters were increased by each of the concentrations of PAF. PAF caused a large rise in venous hematocrit without a corresponding increase in venous plasma protein concentration and a 14- to 37-fold increase in vascular protein flux. Local intra-arterial infusion of PAF promoted leukocyte adherence to mesenteric venular endothelium, a process that is inhibited by the monoclonal antibody, MoAb IB4. PAF-induced increments in intestinal lymph flow, venous hematocrit, and vascular protein flux were greatly attenuated in animals treated with MoAb IB4. The results of this study indicate that PAF promotes the filtration of fluid and protein across intestinal capillaries. These microvascular effects of PAF are mediated, in part, by adherent leukocytes.
Kubes
P
P
Department of Physiology, Louisiana State University Medical Center, Shreveport 71130.
Suzuki
M
M
Granger
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DN
D000818:Animals; D000911:Antibodies, Monoclonal; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D002448:Cell Adhesion / Q000187:drug effects; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects*; D007261:Infusions, Intra-Arterial; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008196:Lymph / Q000187:drug effects / Q000502:physiology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008642:Mesenteric Veins / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D010972:Platelet Activating Factor / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014680:Veins / Q000502:physiology*; D014699:Venules / Q000187:drug effects / Q000473:pathology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D010972:Platelet Activating Factor